Transmembrane activator and CAML interactor explained

Transmembrane activator and CAML interactor (TACI), also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) is a protein that in humans is encoded by the TNFRSF13B gene.

TNFRSF13B is a transmembrane protein of the TNF receptor superfamily found predominantly on the surface of B cells, which are an important part of the immune system.^[1] TACI recognizes three ligands: APRIL, BAFF and CAML.

Function

TACI is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It was originally discovered because of its ability to interact with calcium-modulator and cyclophilin ligand (CAML). TACI was later found to play a crucial role in humoral immunity by interacting with two members of the TNF family: B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL).^[2] These proteins signal through TACI inducing activation of several transcription factors including NFAT, AP-1, and NF-kappa-B which then modulate cellular activities. Defects in the function of TACI can lead to immune system diseases and has shown to cause fatal autoimmunity in mice.^[3]

TACI controls T cell-independent B cell antibody responses, isotype switching, and B cell homeostasis.

Clinical significance

TACI mutations are associated with immunodeficiency in humans, as a significant proportion of common variable immunodeficiency (CVID) patients have TACI mutations. People with this condition produce abnormally low amounts of antibodies, which are needed for protection against infections.

In humans, the gene encoding this protein is located within the Smith–Magenis syndrome region on chromosome 17.^[1]

TACI is currently being targeted for autoimmunity and B cell malignancies via atacicept, a recombinant fusion protein that binds the TACI ligands BAFF and APRIL.^[4]

Interactions

TNFRSF13B has been shown to interact with B-cell activating factor,^{[5] [6]} TRAF6,^[6] TRAF5,^[6] TNFSF13,^[2] TRAF2^[6] and CAMLG.^{[6] [7]}

Further reading

• Bossen C, Schneider P . BAFF, APRIL and their receptors: structure, function and signaling . Seminars in Immunology . 18 . 5 . 263–75 . October 2006 . 16914324 . 10.1016/j.smim.2006.04.006 .
• Treml LS, Crowley JE, Cancro MP . BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells . Seminars in Immunology . 18 . 5 . 297–304 . October 2006 . 16919470 . 10.1016/j.smim.2006.07.001 .
• Mackay F, Leung H . The role of the BAFF/APRIL system on T cell function . Seminars in Immunology . 18 . 5 . 284–9 . October 2006 . 16931039 . 10.1016/j.smim.2006.04.005 .
• Salzer U, Jennings S, Grimbacher B . To switch or not to switch--the opposing roles of TACI in terminal B cell differentiation . European Journal of Immunology . 37 . 1 . 17–20 . January 2007 . 17171762 . 10.1002/eji.200636914 . 321714 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• von Bülow GU, Bram RJ . NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily . Science . 278 . 5335 . 138–41 . October 1997 . 9311921 . 10.1126/science.278.5335.138 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH . TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease . Nature . 404 . 6781 . 995–9 . April 2000 . 10801128 . 10.1038/35010115 . 2000Natur.404..995G . 4323357 .
• Xia XZ, Treanor J, Senaldi G, Khare SD, Boone T, Kelley M, Theill LE, Colombero A, Solovyev I, Lee F, McCabe S, Elliott R, Miner K, Hawkins N, Guo J, Stolina M, Yu G, Wang J, Delaney J, Meng SY, Boyle WJ, Hsu H . TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation . The Journal of Experimental Medicine . 192 . 1 . 137–43 . July 2000 . 10880535 . 1887716 . 10.1084/jem.192.1.137 .
• Seshasayee D, Valdez P, Yan M, Dixit VM, Tumas D, Grewal IS . Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor . Immunity . 18 . 2 . 279–88 . February 2003 . 12594954 . 10.1016/s1074-7613(03)00025-6. free .
• Marsters SA, Yan M, Pitti RM, Haas PE, Dixit VM, Ashkenazi A . Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues BCMA and TACI . Current Biology . 10 . 13 . 785–8 . June 2000 . 10898980 . 10.1016/S0960-9822(00)00566-2 . 2054515 . free . 2000CBio...10..785M .
• von Bülow GU, Russell H, Copeland NG, Gilbert DJ, Jenkins NA, Bram RJ . Molecular cloning and functional characterization of murine transmembrane activator and CAML interactor (TACI) with chromosomal localization in human and mouse . Mammalian Genome . 11 . 8 . 628–32 . August 2000 . 10920230 . 10.1007/s003350010125 . 30311754 .
• Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, Gan Y, Cho YH, Garcia AD, Gollatz E, Dimke D, LaFleur D, Migone TS, Nardelli B, Wei P, Ruben SM, Ullrich SJ, Olsen HS, Kanakaraj P, Moore PA, Baker KP . Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS . The Journal of Biological Chemistry . 275 . 45 . 35478–85 . November 2000 . 10956646 . 10.1074/jbc.M005224200 . free .
• Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE . APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity . Nature Immunology . 1 . 3 . 252–6 . September 2000 . 10973284 . 10.1038/79802 . 6799584 .
• Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF . Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival . Blood . 103 . 2 . 689–94 . January 2004 . 14512299 . 10.1182/blood-2003-06-2043 . free .
• Hymowitz SG, Patel DR, Wallweber HJ, Runyon S, Yan M, Yin J, Shriver SK, Gordon NC, Pan B, Skelton NJ, Kelley RF, Starovasnik MA . Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding . The Journal of Biological Chemistry . 280 . 8 . 7218–27 . February 2005 . 15542592 . 10.1074/jbc.M411714200 . free .
• Moreaux J, Cremer FW, Reme T, Raab M, Mahtouk K, Kaukel P, Pantesco V, De Vos J, Jourdan E, Jauch A, Legouffe E, Moos M, Fiol G, Goldschmidt H, Rossi JF, Hose D, Klein B . The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature . Blood . 106 . 3 . 1021–30 . August 2005 . 15827134 . 2408610 . 10.1182/blood-2004-11-4512 .
• Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS . TACI is mutant in common variable immunodeficiency and IgA deficiency . Nature Genetics . 37 . 8 . 829–34 . August 2005 . 16007086 . 10.1038/ng1601 . 20026177 .

Notes and References

1. Web site: Entrez Gene: TNFRSF13B tumor necrosis factor receptor superfamily, member 13B.
2. Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, Gan Y, Cho YH, Garcia AD, Gollatz E, Dimke D, LaFleur D, Migone TS, Nardelli B, Wei P, Ruben SM, Ullrich SJ, Olsen HS, Kanakaraj P, Moore PA, Baker KP . Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS . The Journal of Biological Chemistry . 275 . 45 . 35478–85 . November 2000 . 10956646 . 10.1074/jbc.M005224200 . free .
3. Seshasayee D, Valdez P, Yan M, Dixit VM, Tumas D, Grewal IS . Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor . Immunity . 18 . 2 . 279–88 . February 2003 . 12594954 . 10.1016/s1074-7613(03)00025-6. free .
4. Cogollo E, Cogollo E, Silva MA, Isenberg D . Profile of atacicept and its potential in the treatment of systemic lupus erythematosus . Drug Design, Development and Therapy . 9 . 1331–9 . March 2015 . 25834391 . 10.2147/dddt.s71276 . 4357613 . free .
5. Yan M, Marsters SA, Grewal IS, Wang H, Ashkenazi A, Dixit VM . Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity . Nature Immunology . 1 . 1 . 37–41 . July 2000 . 10881172 . 10.1038/76889 . 22957179 .
6. Xia XZ, Treanor J, Senaldi G, Khare SD, Boone T, Kelley M, Theill LE, Colombero A, Solovyev I, Lee F, McCabe S, Elliott R, Miner K, Hawkins N, Guo J, Stolina M, Yu G, Wang J, Delaney J, Meng SY, Boyle WJ, Hsu H . TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation . The Journal of Experimental Medicine . 192 . 1 . 137–43 . July 2000 . 10880535 . 1887716 . 10.1084/jem.192.1.137 .
7. von Bülow GU, Bram RJ . NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily . Science . 278 . 5335 . 138–41 . October 1997 . 9311921 . 10.1126/science.278.5335.138 .